Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules

Area of Science:

• Biomedical Engineering
• Chemical Biology
• Medical Imaging

Background:

• pH is a critical physiological parameter frequently altered in diseases such as cancer.
• Hyperpolarized (HP) magnetic resonance spectroscopic imaging offers non-invasive pH monitoring, driving interest in HP-sensors.
• Existing HP-sensors lack comprehensive analysis of biocompatibility, physiological pH sensitivity, and derivatization effects on pKa.

Purpose of the Study:

• To systematically tailor molecular pKa for effective pH biosensing.
• To identify novel biocompatible molecules for HP magnetic resonance pH imaging.
• To elucidate mechanisms for designing targeted in vivo pH probes.

Main Methods:

• Developed a systematic molecular modification approach (carbon chain length, derivatization) to tune pKa.
• Utilized hyperpolarized (HP) magnetic resonance spectroscopic imaging techniques.
• Analyzed biocompatibility, physiological pH sensitivity, and pKa of novel sensor candidates.

Main Results:

• Identified [1-13C]serine amide and [1-13C]-2,3-diaminopropionic acid as novel pH sensors.
• These derivatives exhibit high pH sensitivity (up to 4.8 ppm/pH) with multiple spin-1/2 nuclei (13C, 15N, 31P).
• Demonstrated successful hyperpolarization of 13C spins using dissolution dynamic nuclear polarization (DNP).

Conclusions:

• Novel molecular design strategies can create effective pH biosensors.
• Tailored probes based on modified amino acids show promise for in vivo pH imaging.
• Findings advance the development of targeted magnetic resonance probes for specific physiological pH monitoring.